Caffeine, nicotine, and alcohol are the most prevalent drugs of abuse in our society today. While significant contributions to our understanding of the behavioral effects of nicotine and alcohol have been made in the past decade, relatively little information concerning caffeine's behavioral effects is available. The present project is designed to provide a characterization of the behavioral effects of caffeine. These studies will involve the determination of dose-effect curves for caffeine using both spontaneous locomotor activity and operant behavioral tests in rats. In addition to caffeine, dose-effect curves will be determined for other xanthines (theophylline, theobromine) and other psychomotor stimulants (amphetamine, methylphenidate and nicotine). For the locomotor activity measures, dose-effect curves for these drugs will be determined during the active and inactive portions of the circadian activity cycle. The operant procedures will examine the role of schedule of reinforcement (fixed interval or ratio, variable interval, DRL) in determining sensitivity to xanthines and other psychomotor stimulants. Next, using an operant drug-discrimination paradigm, we propose to determine if caffeine can function as a discriminative stimulus within a dose range comparable to that of human intake. Following determination of the dose-effect curve for caffeine discrimination, we will test for generalization of the caffeine "cue" to the other xanthines and psychomotor stimulants. The caffeine dose-effect curves from the initial behavioral expeiments then will be utilized in an investigation of development of caffeine tolerance and/or dependence. Once tolerance to caffeine has been established, cross-tolerance to the other xanthines and other psychomotor stimulants will be determined. The final phase of this project will attempt to identify possible neuroanatomical loci involved in the discriminative and other behavioral effects of caffeine. In view of the widespread ingestion of caffeine by individuals in various population age groups, the present studies will provide the necessary data base for future studies on the control and behavioral consequences of caffeine intake.